Fatherless Mice Created in Lab

April 22, 2004

Men--who needs them? The sentiment has been voiced by countless lovelorn women, but from a reproductive standpoint, we mammals need males a great deal. Many plants and lower animals, such as insects and reptiles, can reproduce asexually using only maternal DNA through a process termed parthenogenesis. This mechanism does not occur naturally in mammals, and researchers have long been unable to induce it in the laboratory. Now scientists writing in the journal Nature report having created the first fatherless mice, one of which has survived to adulthood and given birth to her own young.

Sexual reproduction combines genetic material from an egg and a sperm, and both copies of DNA contribute equally to the expression of most genes. In a subset of genes regulating development, however, only one copy is turned on. This phenomenon, called genomic imprinting, ensures genetic input from both parents. Because a parthenote contains a double dose of maternal DNA, its genome would not normally activate paternally imprinted genes, hence the failure of mammals to successfully reproduce this way. In earlier experiments, Tomohiro Kono of the Tokyo University of Agriculture and his colleagues knocked out a key maternally imprinted gene, H19, in one strand of DNA taken from an egg cell, and then fused the altered egg with a normal oocyte. Embryos produced this way developed almost to term, but died before birth. In the new work, the researchers achieved success by adding a twist: they further manipulated the DNA to inactivate a mechanism blocking a related paternal gene, Igf2, from switching on in the maternal genome--in effect normalizing the expression of the two genes. To their surprise, altering this pair of genes had a widespread impact on the expression of more than 1,000 other genes, demonstrating the complex role of genomic imprinting in mammalian development. [The mouse pictured above is not one of the "virgin birth" mice discussed in this story.]

Along with the group¿s previous work, the study "provides good evidence that incorrect expression of imprinted genes is one of the major reasons why natural parthenogenesis in mammals has not been possible," write University of Sydney embryologists David A. F. Loebel and Patrick P. L. Tam in an accompanying commentary. Until the function of imprinted genes is better understood, they note, "it seems that the participation of the father in reproduction will remain necessary." --Alla Katsnelson